ABSTRACT
INTRODUCTION Nearly three quarters of a century after the introduction of the potent anti-staphylococcal drug penicillin, Staphylococcus aureus remains a significant bacterial cause of morbidity and mortality in the human population. This gram-positive organism exists as a commensal in the human, residing in the nares or on the skin of approximately one-third of individuals at any time (1,2). The epithelial layer of the skin and mucous membranes proves to be a potent host defense mechanism against staphylococcal infection. A breach of this barrier, however, predisposes the host to a myriad of disease manifestations resulting from S. aureus invasion of the tissues. The remarkable pathogenic potential of this organism has been demonstrated over the past decade, with the rapid spread of highly virulent S. aureus strains worldwide (3-6). A collection of features distinguishes these strains from those previously associated with disease. Most isolates carry the SCCmec IV genetic element that confers resistance to b-lactam antimicrobials, rendering this entire class of antimicrobials obsolete (7). In addition, they demonstrate a novel epidemiologic pattern, frequently being transmitted outside the hospital environment, among otherwise healthy individuals; thus they have been designated community-associated methicillin-resistant S. aureus (CA-MRSA) (8-10). Finally, a growing number of studies have defined unique virulence traits expressed by these strains. The factor that has garnered the majority of attention by virtue of its high degree of epidemiologic association with invasive S. aureus disease is Panton-Valentine leukocidin (PVL), a pore-forming cytotoxin with specificity for leukocytes (11-15). The genes encoding PVL are present on a bacteriophage, a mobile genetic element that contributes to genomic plasticity through horizontal gene transfer (16). Additional phage-encoded proteins that have been demonstrated to contribute to the virulence phenotype include the plasminogen activator staphylokinase (Sak) (17-19), the immunomodulatory proteins CHIPS (chemotaxis inhibiting protein) and SCIN (staphylococcal complement inhibitor) (20-22). Most recently, Wang et al., have defined a novel class of secreted staphylococcal peptides termed ‘‘phenol-soluble modulins’’ (PSMs) that are highly expressed in current CA-MRSA isolates, and contribute to the destruction of human neutrophils (23). While it is unlikely that a single factor in CA-MRSA strains is solely responsible for the high virulence phenotype, it is readily appreciated that a constellation of pathogenic traits may render these strains more capable of causing significant infection in healthy hosts.
